The Research Progress in Immunotherapy of Tuberculosis

Tuberculosis (TB) is a serious public health problem worldwide. The combination of various anti-TB drugs is mainly used to treat TB in clinical practice. Despite the availability of effective antibiotics, effective treatment regimens still require long-term use of multiple drugs, leading to toxicity, low patient compliance, and the development of drug resistance. It has been confirmed that immune recognition, immune response, and immune regulation of Mycobacterium tuberculosis (Mtb) determine the occurrence, development, and outcome of diseases after Mtb infection. The research and development of TB-specific immunotherapy agents can effectively regulate the anti-TB immune response and provide a new approach toward the combined treatment of TB, thereby preventing and intervening in populations at high risk of TB infection. These immunotherapy agents will promote satisfactory progress in anti-TB treatment, achieving the goal of “ultra-short course chemotherapy.” This review highlights the research progress in immunotherapy of TB, including immunoreactive substances, tuberculosis therapeutic vaccines, chemical agents, and cellular therapy.

Efficacy and safety of short course chemotherapy regimens in older children and adolescents with multiple and extensive drug resistant respiratory tuberculosis

The objective of the study: to evaluate the efficacy and safety of short course chemotherapy regimens for multiple/extensive drug resistant tuberculosis of the respiratory system (MDR/XDR) in older children and adolescents.Subjects and Methods. A cohort prospective controlled study (2017 to 2019) included 23 patients from 13 to 17 years old with various clinical forms of respiratory tuberculosis with multiple/extensive drug resistance.Results. In 22 out of 23 cases, the following chemotherapy regimen was used: 6 months - the intensive phase / 6 months - the continuation phase, in one patient – 3 months of the intensive phase / 9 months of the continuation phase. In 15 out of 23 cases, the chemotherapy regimens in the intensive phase, taking into account the MBT drug sensitivity test, consisted of 5 drugs, in 8 cases – of 4 drugs. During the continuation phase, all patients received 3 drugs. Of the 23 patients, 8 patients used bedaquiline in short course chemotherapy regimens: 2 – 1 course, 6 – 2 courses.Conclusion. The possibility of reducing the main course of chemotherapy for MDR/XDR TB in children and adolescents to 12 months instead of 18-24 months has been proved.

Efficacy and safety of short-term chemotherapy for patients with spinal tuberculosis undergoing surgery in Chinese population: a meta-analysis

Objective The aim of this meta-analysis was to systematically evaluate the clinical efficacy and safety of short-course chemotherapy (≤ 6 months) compared with the standard therapy (9–18 months) for patients with spinal tuberculosis (TB) undergoing surgery in Chinese population. Methods In this meta-analysis, we searched electronic databases in the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang data to determine the equivalence of short-course therapy (group A) and standard therapy (group B) for the drug therapy of TB in Chinese population up to December 24, 2019. Weighted mean difference (WMD), odds risk (OR), and their 95% confidence interval (CI) were calculated. All analyses of relevant outcome indicators were managed by using the Review Manager (RevMan) 5.2 software. Results This meta-analysis included six trials published involving 851 patients (group A, 397; group B, 454) with spinal TB. Results showed there were no significant differences between group A and group B in clinical cure rate (OR = 0.61; 95% CI 0.19–2.00, p > 0.05), change of erythrocyte sedimentation rate (ESR) (WMD = − 0.75; 95% CI − 3.33 to 1.83; p > 0.05) and bone graft fusion rate (OR = 2.32; 95% CI 0.36–14.81, p > 0.05). Meanwhile, there were fewer side effects (OR = 0.37; 95% CI 0.24–0.58, p < 0.05) in group A compared with group B. Conclusions The results of this meta-analysis showed that for patients with spinal TB undergoing surgery in Chinese population, short-course chemotherapy could be equivalent to the standard chemotherapy in terms of efficacy and have less side effects than the latter.

Short course chemotherapy in children suffering from drug resistant tuberculosis

The objective: to study the effect of short course chemotherapy regimens on treatment outcomes in children with drug resistant tuberculosis.Subjects and methods. In 2017-2019, 31 children at the age from 3 to 17 years old, received short course chemotherapy which lasted for 12-15 months. Children of both genders were enrolled in the study, they all were new pulmonary tuberculosis cases with multiple drug resistance or at risk of MDR, with no history of previous treatment with reserve anti-tuberculosis drugs, and without severe concomitant diseases. Before the treatment was prescribed, all children underwent lung computed tomography additionally to general clinical and laboratory tests.Results. The chemotherapy regimen for each child consisted of 4-6 drugs selected individually with the consideration of resistance pattern of the child or suspected index case. In all cases, the combination of drugs included fluoroquinolones (levofloxacin or moxifloxacin). Amikacin (67.7%), aminosalicylic acid (80.6%) and prothionamide (74.2%) were frequently prescribed. 54.8% of children received pyrazinamide and 48.4% – cycloserine. Given the limited lesions, only 16.1% of children received linezolid and 9.7% of children received bedaquiline. The main chemotherapy course made 13.2 ± 0.5 months (from 12 to 15 months depending on the form of tuberculosis and changes during treatment). The duration of the intensive phase made 4.8 ± 0.3 on the average. 2 (6.5 ± 4.4%) of 31 children developed adverse events requiring the cancellation of the drugs causing them.Conclusion. This study has demonstrated satisfactory tolerability and good efficacy of these short course regimens for treatment of multiple drug resistant tuberculosis. No relapses of tuberculosis were reported.

Nouveau short-course therapy and morphism mapping for clinical pulmonary Mycobacterium kansasii

Standard therapy [isoniazid, rifampin, ethambutol], with or without a macrolide, for pulmonary Mycobacterium kansasii lasts more than a year. Therefore, shorter treatment duration regimens are required. We used data from 32 Taiwanese patients treated with standard therapy who were followed using repetitive sampling-based sputum Mkn time-to-positivity in liquid cultures to calculate kill slopes [γ] based on ordinary differential equations and time-to-extinction of each patient’s bacterial burden. The γ was 0.18 [95% Confidence Interval (CI): 0.16-0.20] log10 CFU/mL/day on standard therapy. Next, we identified Mkn time-to-extinction in the hollow fiber system model of pulmonary M. kansasii disease [HFS-Mkn] treated with standard therapy, which was a γ of 0.60 [95% CI: 0.45-0.69) log10 CFU/mL/day. The γs and time-to-extinctions between the two datasets formed structure-preserving maps based on category theory: thus, we could map them from one to the other using morphisms. This mapping identified a multistep non-linear transformation-factor for time-to-extinction from HFS-Mkn to patients. Next, a head-to-head study in the HFS-Mkn identified median time-to-extinction for standard therapy of 38.7 [95% CI: 29.1-53.2) days, isoniazid-rifampin-ethambutol-moxifloxacin of 21.7 [95% CI: 19.1-25) days, isoniazid-rifampin-moxifloxacin of 22 [96% CI: 20.1-24.5) days, and rifampin-moxifloxacin-tedizolid of 20.7 [95% CI:18.5-29) days. Our transformation-factor based translation predicted the proportion of patients of 90.7 [88.74-92.35)% achieving cure with standard therapy at 12 months, and 6-months cure rates of 99.8 [95% CI: 99.27-99.95)% for isoniazid-rifampin-ethambutol-moxifloxacin, 92.2 [90.37-93.71)% for isoniazid-rifampin-moxifloxacin, and 99.9 [99.44-99.99)% for rifampin-moxifloxacin-tedizolid. Thus, rifampin-moxifloxacin-tedizolid and isoniazid-rifampin-ethambutol-moxifloxacin are predicted to be short-course chemotherapy regimens for pulmonary M. kansasii disease.

Clinical efficacy and safety of ultra-short-course chemotherapy in treatment of spinal tuberculosis after complete debridement: an observational study

Objective To evaluate the clinical efficacy and safety of ultra-short-course chemotherapy (<4 months) in treating spinal tuberculosis following complete debridement. Methods Clinical data of patients diagnosed with spinal tuberculosis, who underwent surgery with postoperative chemotherapy for < 4 months at the General Hospital of Ningxia Medical University between January 2005 and March 2015, were retrospectively analysed. Clinical manifestations, American Spinal Injury Association grades, states of bone fusion and lesion healing, deformity correction, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and adverse drug reactions, observed before and after surgery and at the final follow-up, were assessed. Results Sixty patients were included, comprising 26 male and 34 female patients aged 16–78 years (mean, 40.85 years). Patients received postoperative chemotherapy for 3–4 months (mean, 3.61 months) and were followed for 25–129 months (mean, 70.61 months). Spinal tuberculosis recurred after surgery in one patient, who was cured by subsequent surgery. At the final follow-up, no symptoms of tuberculosis, local pain, abscess or sinus were observed. Daily life and working abilities were almost recovered in all patients. ESR and CRP levels were restored to normal, bone grafts fused, lesions healed and neurological functions were recovered. Postoperative chemotherapy-induced complications occurred in 10 patients (16.67%). Conclusions Complete debridement plus ultra-short-course chemotherapy for 3–4 months may be safe and efficacious in treating spinal tuberculosis, and requires further investigation.

Between Donor Interest, Global Models and Local Conditions: Treatment and Decision-Making in the Somalia-Finland Tuberculosis Control Project, 1981–3

Despite numerous global health initiatives after World War II, tuberculosis still poses a major threat in sub-Saharan Africa. This article examines one attempt to tackle this problem: the Somalia-Finland Tuberculosis Control Project. Conducted in the 1980s as a bilateral development aid project between the two countries, it became the most extensive – and expensive – tuberculosis initiative in Somalia in that decade. An interesting feature of the project is that, despite a lack of previous experience in tuberculosis work in developing countries, the Finnish partner decided not to follow the WHO global guidelines designed to standardise tuberculosis activities across the developing world. Instead, Finns established their own treatment programme based on X-ray and short-course chemotherapy – otherwise rarely used in clinical practice in Africa. Through a close reading and comparison of the correspondence, project plans, memos and minutes, the article analyses the formation of this strategy. Focusing on ground-level decision-making, it argues that the decisions were based not only on a belief in the superior clinical effectiveness of these methods, but also on the fact that they better suited Finnish ambitions and project logic. Thus, the article supports the notion that donor perspectives on resources and project objectives determined what was seen as feasible treatment in a developing country. By shedding light on the debate between the supporters of short-course chemotherapy and the WHO standard treatment strategy, it also contributes to the early history of DOTS (directly observed treatment, short course).